I am a senior researcher in the group of Professor Lennart Hammarström at the Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine. I am supervising the Immunotherapy group and my research focus on passive immunization using Lactobacillus expressing antibody fragments against mucosal pathogens.
1987-1990 B.Sc. in Microbiology, Department of Biochemistry, Université Laval, Canada
1990-1992 M.Sc. in Microbiology, Department of Biochemistry, Université Laval, Canada
1992-1997 Ph.D. in Microbiology and Immunology, Faculty of Medecine, Université Laval, Canada
Thesis (Msc and PhD):
Harold Marcotte. “Étude de la variabilité dans les interactions hôte-bactéries chez la souris BALB/c ”, Thèse (MSc), Université Laval, 1992. http://worldcat.org/oclc/77357770
Harold Marcotte. “Interactions entre les IgA salivaires et la microflore buccale chez la souris”, Thèse (PhD), Université Laval, 1997.
Passive administration of antibodies represents the therapy of choice for mucosal infections, particularly in children and immunocompromised individuals and during the past two decades, oral administration of polyclonal antibodies against selected enteric pathogens has been employed successfully. However, production and purification of these antibodies is costly and therefore, efforts have been made to develop new methods for production of monoclonal antibodies or antibody fragments employing plant, yeast and bacterial systems.
An attractive idea is to use lactobacilli as vectors for in situ delivery of antibody fragments and other therapeutic molecules at mucosal surfaces. Lactobacilli are Gram-positive bacteria with a long history of safe use in food fermentation and preservation. They are also a significant component of the naturally occuring gastrointestinal and vaginal microbiota. The desired genes can be integrated into the bacterial genome, creating food grade, genetically modified lactobacilli. The modified lactobacilli can be freeze-dried or spray dried and subsequently incorporated in capsules or food products. We have previously shown that genetically modified lactobacilli delivering antibody fragments against S. mutans (Krüger et al. 2002), rotavirus (Pant et al. 2006, Alvarez et al. 2015), and C. difficile (Andersen et al. 2015) are protective in animal models. In addition, lactobacilli can be used to deliver a ranged of therapeutic molecules in the gastrointestinal tract such as cytokines, antimicrobial peptides and glucacon-like peptides.
Our current research projects include:
- Generation of antibody fragments against mucosal pathogens
- Delivery of antibody fragments against mucosal pathogens (norovirus, HIV) by lactobacilli
- Lactobacilli delivering cytokines (IL-10, IL-21, IL-22) and CD40L for treatment of inflammatory diseases and IgA deficiency
- Treatment of bacterial vaginosis using a combination of antibiotics and probiotics
I have always been employed to conduct 100% research since I began as a postdoctoral fellow at KI and all teaching performed has been on an invited basis.
I am currently teaching immunology for the Biomedicine Laboratory Science program (Biomedicinska analytikerprogrammet).
I am also currently supervising one visiting PhD student.